Poster Presentation 4th Metabolic Diseases; Breakthrough Discoveries in Diabetes & Obesity Meeting 2024

Mechanistic insights into postprandial insulin-glucagon interactions and their impact on glycaemic excursions following protein-glucose co-ingestion in humans (#171)

Giang M Dao 1 , Chris S Shaw 2 , Andrew C Betik 2 , Vicky Kuriel 2 , Clinton R Bruce 2 , Greg M Kowalski 1
  1. Institute for Physical Activity and Nutrition, Metabolic Research Unit, School of Medicine, Deakin University, Geelong, Victoria, Australia
  2. Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia

It is generally regarded that insulin lowers blood glucose by suppressing endogenous glucose production (EGP) and stimulating glucose uptake (Rd), while glucagon increases glucose by stimulating EGP. Interestingly, protein and glucose co-ingestion stimulates both insulin and glucagon secretion, yet glucose excursions are typically reduced compared to ingesting glucose alone. Despite stimulating glucagon secretion, it is unclear why protein ingestion can lower glucose excursions. Using the triple stable isotope glucose tracer technique to measure postprandial glucose fluxes, this study aimed to address this question. Eleven healthy adults (5M/6F, 27±1.5 years, BMI: 23.4±0.6 kg/m2) underwent three separate trials in random order, ingesting either 25g glucose (25G;~100 kcal), 50g glucose (50G;~200kcal) or 25g glucose plus 25g whey protein (25WG;~200kcal), allowing comparisons to be made under both glucose and calorie matched conditions.

Glucose excursions were markedly lower during the 25WG condition (p<0.001). As expected, 25WG increased glucagon concentrations (~3-fold), while 25G and 50G reduced them. Insulin and GIP were markedly higher during 25WG vs 25G conditions (p<0.01), while GLP-1 was similar. Under calorie matched conditions (25WG vs 50G), 25WG produced higher peak insulin concentrations (p=0.04) while GIP and GLP-1 responses were similar. EGP was less suppressed for 25WG (~48% suppressed) compared to 25G (~70% suppressed) or 50G (79% suppressed) conditions (p<0.001). Surprisingly, compared to 25G, 25WG did not enhance Rd, but rather reduced the early (30-60 min) phase of glucose absorption.  

The findings confirm that protein-glucose co-ingestion can robustly stimulate glucagon secretion while also enhancing the GIP and insulin response, which is accompanied by robustly lower postprandial glucose excursions. For the first time, we reveal that protein co-ingestion can lower glycaemic excursions despite interfering (probably due to glucagon) with EGP suppression. Despite the greater insulin response, the net glycaemic benefit from protein co-ingestion appears to come from reduced early glucose absorption, not enhancement of Rd.